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Vesicoureteral reflux (VUR) is defined as the urine backflow from the urinary bladder to the pyelo-caliceal system. In contrast, intrarenal reflux (IRR) is the backflow of urine from the renal calyces into the tubulointerstitial space. VURs, particularly those associated with IRR can result in reflux nephropathy when accompanied by urinary tract infection (UTI). The prevalence of IRR in patients with diagnosed VUR is 1–11% when using voiding cystourethrography (VCUG), while 11.9–61% when applying the contrast-enhanced voiding urosonography (ceVUS). The presence of IRR diagnosed by VCUG often correlates with parenchymal scars, when diagnosed by a 99mTc dimercaptosuccinic acid scan (DMSA scan), mostly in kidneys with high-grade VURs, and when diagnosed by ceVUS, it correlates with the wide spectrum of parenchymal changes on DMSA scan. The study performed by both ceVUS and DMSA scans showed IRRs associated with non-dilated VURs in 21% of all detected VURs. A significant difference regarding the existence of parenchymal damage was disclosed between the IRR-associated and IRR-non-associated VURs. A higher portion of parenchymal changes existed in the IRR-associated VURs, regardless of the VUR grade. That means that kidneys with IRR-associated VURs represent the high-risk group of VURs, which must be considered in the future classification of VURs. When using ceVUS, 62% of places where IRR was found were still unaffected by parenchymal changes. That was the basis for our recommendation of preventive use of long-term antibiotic prophylaxis until the IRR disappearance, regardless of the VUR grade. We propose a new classification of VURs using the ceVUS method, in which each VUR grade is subdivided based on the presence of an IRR. [ABSTRACT FROM AUTHOR]

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Vesicoureteral reflux (VUR) is defined as the urine backflow from the urinary bladder to the pyelo-caliceal system. In contrast, intrarenal reflux (IRR) is the backflow of urine from the renal calyces into the tubulointerstitial space. VURs, particularly those associated with IRR can result in reflux nephropathy when accompanied by urinary tract infection (UTI). The prevalence of IRR in patients with diagnosed VUR is 1–11% when using voiding cystourethrography (VCUG), while 11.9–61% when applying the contrast-enhanced voiding urosonography (ceVUS). The presence of IRR diagnosed by VCUG often correlates with parenchymal scars, when diagnosed by a 99mTc dimercaptosuccinic acid scan (DMSA scan), mostly in kidneys with high-grade VURs, and when diagnosed by ceVUS, it correlates with the wide spectrum of parenchymal changes on DMSA scan. The study performed by both ceVUS and DMSA scans showed IRRs associated with non-dilated VURs in 21% of all detected VURs. A significant difference regarding the existence of parenchymal damage was disclosed between the IRR-associated and IRR-non-associated VURs. A higher portion of parenchymal changes existed in the IRR-associated VURs, regardless of the VUR grade. That means that kidneys with IRR-associated VURs represent the high-risk group of VURs, which must be considered in the future classification of VURs. When using ceVUS, 62% of places where IRR was found were still unaffected by parenchymal changes. That was the basis for our recommendation of preventive use of long-term antibiotic prophylaxis until the IRR disappearance, regardless of the VUR grade. We propose a new classification of VURs using the ceVUS method, in which each VUR grade is subdivided based on the presence of an IRR.

Objective To explore the value of contrast-enhanced voiding urosonography (CeVUS) in the diagnosis of vesicoureteral reflux (VUR) and urethrovaginal diseases in children. Methods From September 2020 to December 2021, the relevant clinical data were retrospectively reviewed for 207 children with suspected VUR examined by CeVUS. And CeVUS was performed by SonoVue (Bracco, Italy) and intravesical administration via catheter while urethrovaginal examinations were performed in girls. According to the international VUR grading system, VUR was divided into five grades. Grade of VUR, presence of intrarenal reflux (IRR) and abnormal findings of urethrovaginal tract were recorded, .And the diagnostic value of CeVUS was examined in children with VUR and urethrovaginal abnormalities. Eighteen patients were examined by voiding cystourethrogram (VCUG) during the same period. Weighted Kappa test was utilized for comparing the consistency of CeVUS and VCUG in diagnosis of VUR. Results A total of 416 pyeloureteral units (PUUs) were examined in 207 children, including duplicate kidney (n=3) and unilateral renal absence (n=1). No adverse events related to contrast agent were reported. Among them, 97 (97/207, 46.86%) were diagnosed with VUR. Among 416 PUUs, 145(145/416, 34.86%) were diagnosed as VUR. Twenty-four IRR occurred in grade Ⅲ and above. Among 18 children examined by CeVUS and VCUG at the same time (2 duplicate kidneys & 1 unilateral kidney absence, a total of 37 PUUs), Weighted Kappa value of VUR consistency was 0.747 (P<0.01, 95%CI: 0.554-0.941). Among 37 PUUs, 12 PUUs had IRR on CeVUS, one VUR in lower pole of duplex kidney missed a diagnosis by VCUG. Also there were urethrovaginal abnormalities (n=5), Y-shaped ureter (n=1) and miniature kidney at reflux side (n=6). Conclusion CeVUS is safe and has high consistency with VCUG. CeVUS has advantages over VCUG in the diagnosis of IRR and duplicate kidney with VUR. CeVUS can also detect urethrovaginal abnormalities. CeVUS can be used as the preferred imaging method for VUR in children. [ABSTRACT FROM AUTHOR]

Contemporary videourodynamic (VUD) investigation combines voiding cystourethrography (VCUG) and urodynamics into one study, which allows simultaneous visualization of the urinary tract by ionizing radiation alongside the measurement of sensation, capacity, compliance, and detrusor pressure during bladder filling and voiding using one double lumen catheter. Today VUD is a benchmark for evaluating the lower urinary tract disorders in children because it evaluates urinary bladder and sphincter function and visualizes bladder morphology and vesicoureteral reflux (VUR) presence at the same time. Several previous studies of fluoroscopic videourodynamics issued concerns regarding radiation exposure. This technical report aims to describe a new modality of VUD in children by replacing fluoroscopic VCUG with contrast-enhanced voiding urosonography (ceVUS). ceVUS using second-generation contrast media and harmonic imaging is a radiation-free and highly sensitive imaging modality used to detect VUR in children. We simultaneously performed an infusion of ultrasound contrast through the double lumen urodynamic catheter during urodynamic evaluation. This article describes the advantages of this method compared with a conventional technique. In addition to being radiation-free, this procedure of advanced videourodynamics method can better detect vesicoureteral reflux and intrarenal reflux combined with urodynamic disorders associated with VUR. [ABSTRACT FROM AUTHOR]

Scar development in the children’s renal cortex with vesicoureteral reflux (VUR) is one of the most important parameters of prognosis. It can develop regardless of the chosen treatment, even after the regression of VUR. The shape of the renal papillae, the ascending urinary tract infection, the greater than third-degree VUR, and finally the increased intra-calyceal pressure, induce the formation of renal scarring in the renal parenchyma. Renal scarring may complicate VUR independently of the therapeutic strategy (conservative or operative) and its regression. For restitution of this entity, many scientific terms have been used and the most common of them is intrarenal reflux (IRR). The effects of VUR on future renal function result from the limited ability of the affected kidney to grow (failure of renal growth) due to the existence of scars in the renal cortex, the worsening of these scars, or finally the creation of new scars. With the present study, we intend to clarify the etiology and the pathophysiology of IRR and the relation of VUR prognosis to newer biomarkers such as N-acetyl-beta-glycosaminidase, beta-2 microglobulin, Pentraxin- 3 and Liver-type fatty-acid-binding protein. [ABSTRACT FROM AUTHOR]

Background: Intrarenal reflux may be seen with vesicoureteral reflux (VUR) when contrast from the pelvocalyceal system extends into tubules in the parenchyma. Because intrarenal reflux has been associated with scarring, detecting intrarenal reflux may influence management to avoid renal damage. Objective: Our objective was to evaluate the prevalence of intrarenal reflux identified on contrast-enhanced voiding urosonography (ceVUS) and its association with sex, age, grade of VUR, location in kidney and stage of bladder filling or voiding. Materials and methods: CeVUS studies performed from August 2019 through July 2020 with VUR were retrospectively reviewed by two pediatric radiologists. They independently graded VUR and assessed for intrarenal reflux, noting its location and stage of bladder filling or voiding during which it occurred. The presence and location of scarring was also recorded. Results: One hundred and six ceVUS exams were reviewed with 211 kidneys evaluated (one solitary kidney). Patients were ages 2 weeks to 12 years (mean: 1.8 years) with 71 females (67%) and 35 males (33%). Grades 2 to 5 VUR were detected in 165 kidneys with intrarenal reflux seen in 42 (25.4%). Intrarenal reflux was present in 1 of 40 kidneys (2.5%) with grade 2, 10 of 67 (14.9%) with grade 3, 25 of 47 (53.2%) with grade 4 and 6 of 11 (54.5%) with grade 5 VUR. Intrarenal reflux occurred during voiding in 31 of 42 kidneys (73.8%) and was seen most often in the lower pole (71.4%) with significant association between intrarenal reflux and interpolar renal scarring (odds ration [OR] 3.92; 95% confidence interval [CI] 1.49, 10.32; P-value 0.01). Conclusion: Intrarenal reflux was often seen on ceVUS, with the highest frequency occurring in young patients with grades 4 and 5 VUR and during voiding. Radiologists should have a high index of suspicion for intrarenal reflux on ceVUS, especially in young children with high-grade VUR. [ABSTRACT FROM AUTHOR]

Purpose This study evaluated the diagnostic performance of contrast-enhanced voiding ultrasonography (CeVUS) for detecting intrarenal reflux (IRR) and the correlation between CeVUS-detected IRR sites and photon defect sites in acute 99mTc-dimercaptosuccinic acid (DMSA) renal scans in pediatric patients. Methods Fifty-four kidneys from 27 patients (20 males and seven females; mean age, 5.6±4.1 months) who underwent CeVUS and acute DMSA renal scans for recurrent urinary tract infection (UTIs) or pyelonephritis were included. Pediatric experts compared the results of CeVUS with acute DMSA renal scans. Results Thirteen renal units (13/54, 24.1%) in 10 patients (nine males and one female; mean age, 6.3±3.7 months; age range, 0 to 13 months) showed vesicoureteral reflux and eight renal units (8/54, 14.8%) demonstrated IRR on CeVUS. Ten renal units in eight patients (six males and two females; mean age, 6.9±1.4 months; age range, 2 to 13 months) showed 19 photon defects on acute DMSA renal scans. Fifty-two renal units (96.3%) showed concordant results, and two renal units (3.7%) showed discordant results between CeVUS and acute DMSA renal scans. IRR accounted for 15/19 (78.9%) photon defects in eight renal units of seven patients using CeVUS. In a per-renal-unit analysis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CeVUS were 80%, 100%, 100%, 95.7%, and 96.3%, respectively. Conclusion CeVUS showed good performance in detecting IRR, and the IRR sites detected by CeVUS closely correlated with photon defect sites in acute DMSA scans. CeVUS may play an important role in managing patients with recurrent UTIs or pyelonephritis with reduced radiation exposure.

Purpose This study evaluated the diagnostic performance of contrast-enhanced voiding urosonography (ce-VUS) using a second-generation ultrasound contrast agent for the diagnosis of vesicoureteral reflux (VUR) and intrarenal reflux (IRR), and compared it with that of standard fluoroscopic voiding cystourethrography (VCUG). Methods Thirty-two consecutive children from April to October 2019 were included in this study. ce-VUS and VCUG were performed simultaneously by two operators with intravesical infusion of a mixture of ultrasound contrast medium, iodinated contrast medium and water. Two pediatric radiologists independently reviewed the ce-VUS and VCUG images and reported the presence and degree of VUR (grades I-V), and the presence and type of IRR. Results Twenty-seven of 63 urinary systems showed VUR. Interobserver agreement for VUR grading was very good for both examinations (κ=0.87; 95% confidence interval [CI], 0.82 to 0.92 for ce-VUS and κ=0.92; 95% CI, 0.87 to 0.96 for VCUG). The detection rate of VUR showed no significant difference between the two examinations (P=0.370). Four cases of VUR were missed on ce-VUS, while one case of VUR was missed on VCUG. All four false-negative cases on ce-VUS were grade 1 VUR. The two examinations showed very good agreement regarding VUR grading (κ =0.89; 95% CI, 0.81 to 0.96). IRR was more frequently detected with ce-VUS than with VCUG (10 cases with ce-VUS vs. 3 cases with VCUG, P=0.016). Conclusion ce-VUS showed very good agreement with VCUG for detecting grade 2 VUR and above, while grade 1 VUR was sometimes missed with ce-VUS. IRR was more frequently detected with ce-VUS than with VCUG.

PurposeTo describe the parenchymal defects in kidneys with intrarenal reflux (IRR) diagnosed using contrast-enhanced voiding urosonography (ceVUS) and 99mTc-DMSA scintigraphy (DMSA scan).Materials and MethodsA group of 186 uretero-renal units (URUs) was analyzed using ceVUS and DMSA scans: 47 without vesicoureteral reflux (VUR) (group A) and 139 with VURs, comprising 73 VURs without (group B), and 66 with IRR (group C). VURs included non-dilating (grades I–II), mildly non-dilating (grade III), and non-dilating (grades IV–V) grades. The parenchymal changes were analyzed using a DMSA scan.ResultsThe median age for VUR diagnosis was 16.5 months in girls, and 8.5 months in boys (Z = 3.9; p = 0.001). IRR occurred in 51.4% of boys and in 25.9% of girls (χ2 = 12.4; p < 0.001). The non-dilating VUR occurred in 44% of boys and 24.1% of girls (χ2 = 7.7; p = 0.005). IRRs characterized upper and lower renal segments (81.8 and 63.6%) and middle segments (33.3%). Both incidence and increase in IRR correlated with the grade of VUR (p < 0.001). The incidence of reduced DMSA signal was statistically different among groups A + B and C, but not between groups A and B (χ2 = 32.2; p < 0.001). No statistically significant relationship existed between the reduced DMSA signal and the grade of VUR in group C. The reduced DMSA signal appeared in 9.9% positions in kidneys from group A, 14% from group B, and 32% from group C. Out of all 118 IRRs, 38.1% had reduced and 61.9% had normal DMSA signal. Among 11 parenchymal scars found in all three groups, 2 belonged to group B, 9 to group C, while group A had no scars.ConclusionThe parenchymal changes are the most prominent in the group with IRR, but they do not significantly differ among kidneys with different grades of VUR. VURs of higher grades are associated with a higher incidence of IRR and early clinical presentation. Scars can also appear in lower-grade VURs accompanied by IRR. Boys with VUR have earlier clinical presentation than girls, as they have significantly higher grades of VUR with a higher proportion of IRRs. Therefore, we suggest a subdivision of VURs into those with IRR and abundant parenchymal damage, and those without IRR and less parenchymal damage.

Purpose: Although contrast-enhanced urosonography (ceVUS) has shown capable diagnostic accuracy for the diagnosis of vesicoureteral reflux (VUR) in children, the ability of ceVUS to detect intrarenal reflux (IRR) is considered limited. The purpose of our study is to assess the ability of ceVUS to detect IRR as well as its association with age, gender, and the grade of VUR. Methods: This study included 5153 children who were referred to our clinic for ceVUS. All children underwent sonographic examinations, which were performed on a LOGIQ S8 machine equipped with dedicated software for contrast-enhanced studies with harmonic imaging. Standard ultrasound of the urinary tract was followed by bladder catheterisation and instillation of physiological normal saline and the US contrast medium (SonoVue®, Bracco). Results: VUR was diagnosed by ceVUS in 1959 out of 5153 children (38%), of whom IRR was found in 233 of 1959 children (11.9%). A total of 285 ureteral units showing IRR were found. High grades of VUR (IV + V) with IRR were found in a total of 235 of 285 (82.81%) renal units. Bilateral IRR was found in 53 patients, usually with a high-grade VUR on both sides. Most children had VUR grade IV, predominantly those < 12 months. The younger the child, the higher the likelihood of higher-grade VUR (p = 0.02). Conclusion: ceVUS, combined with harmonic imaging and second-generation ultrasound contrast media, enabled IRR detection in almost 12% of our patients with VUR. IRR is most commonly found in children under 1 year of age with VUR grades IV and V. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to analyze the incidence of intrarenal reflux (IRR) among vesicoureteral refluxes (VURs), diagnosed by contrast-enhanced voiding urosonography (ceVUS), to define VURs which are positive to IRR and their locations in the kidney.Materials and Methods: Seventy patients with VURs, including 103 uretero-renal units (URUs) with VURs of grades II–V (37 URUs were excluded because of renal anomalies or absence of VUR) were examined with ceVUS due to recurrent febrile UTI or first febrile UTI accompanied by abnormalities on renal ultrasonography. Patients were examined on GE Logiq S8 ultrasound machine, using second generation of ultrasound contrast agent.Results: Out of 103 VURs, 51 (49.51%) had IRR regardless the grade of VUR, showing increase in IRR incidence with VUR severity (p < 0.0001). The median age at the time of IRR diagnosis was 5 months (IQR, 3–14.3), whereas in patients without IRR, it was 15.5 months (IQR, 5–41.5), (p = 0.0069). IRR was most common in superior pole (80%), followed by inferior pole (62.7%), and middle segments (37%), and to all segments (27%) (p < 0.0001).Conclusion: In the present study, patients with IRR-associated VUR showed earlier clinical presentation. The distribution of IRRs corresponded to the natural distribution of composed papillae types II and III, while the incidence of IRR increased with severity of VUR. Further clinical studies may point to the importance of considering IRR in the future classification of VUR.

The intrarenal reflux is caused by impaired emptying of the renal pelvis, that leads to increased intrarenal pressure. Increased pelvis pressure can be the result of a variety of states. The most common causes are acute upper urinary tract obstruction or overfilling of the pelvis during retrograde intrarenal surgery (RIRS) or retrograde pyelography. In rare cases, it is due to impaired neuromuscular tone of the upper urinary tract that leads to hyperkinetic state. We have presented case with a 73-year-old patient with intrarenal reflux into the peripelvic renal cysts. Since no such cases were found in the literature, this observation is unique.

Objective - Intrarenal reflux (IRR) is the main cause of renal injury in children with vesicoureteral reflux (VUR), and has an important role in the pathogenesis of scarring and reflux nephropaty (RN). Using voiding cystourethrography (VCUG) IRR is usually detected in high grades of VUR. Our case demonstrates the possibility of visualizing IRR in a child with low-grade VUR using contrast-enhanced voiding urosonography (ceVUS). Case Report - We report the case of a four-month-old girl with Klebsiella pneumoniae febrile urinary tract infection (UTI) who was diagnosed by ceVUS with VUR grade II on the right kidney, with IRR strongest in the lower pole. A 99m Tc 2.3-dimercaptosuccinic acid (DMSA) renal scan, which was performed 8 months after the UTI revealed a small scar on the lower pole of the right kidney, where IRR was found by ceVUS. Conclusion - Our case report showed that not only the grade of reflux but also the presence of IRR is important to predict the severity of the clinical picture and the development of possible scarring. It is important to find IRR because it may be connect with renal scars. VUR with IRR should be managed actively to decrease the chances of renal scarring or the development of new scars. [ABSTRACT FROM AUTHOR]

Background: The significance of intrarenal reflux as a risk factor for renal scarring and hypertension has been discussed. Fluoroscopic detection of intrarenal reflux depends on the equipment, the training of the radiologists and the timing of spot film acquisition.Objective: To evaluate the prevalence of intrarenal reflux and its association with age, gender, grade of vesico-uretero-renal reflux and the renal segments affected.Materials and Methods: We retrospectively analysed 1,166 voiding cysturethrographies. Patients' ages ranged from 1 day old to 19 years old. Vesico-uretero-renal reflux was detected in 209 female and 164 male patients using a standardised technique with digital pulsed fluoroscopy. The point in time and grade of reflux were documented with spot films. All radiographs showing reflux were assessed for the occurrence of intrarenal reflux.Results: Intrarenal reflux was detected in 41 of 373 (11%) patients with vesico-uretero-renal reflux. Unilateral intrarenal reflux was found in 30 patients and bilateral in 11. The left kidney was more frequently affected than the right (31 versus 21). Only patients younger than 9 years of age were affected (mean age: 1.6 years, median: 0.8 years). Intrarenal reflux was independent of gender and was most frequently observed in grade IV reflux (59.6%) and less often in grade V (23.1%) and grade III (17.3%).Conclusion: Intrarenal reflux in this study was detected in 11% of patients with vesico-uretero-renal reflux, predominantly with reflux grade IV and in patients younger than 4 years old. [ABSTRACT FROM AUTHOR]

Background: Voiding cystourethrography continues to be the gold standard in the diagnostics of a wide range of diseases of the urinary tract in children., Material and Methods: Indications, implementation of voiding cystourethrography in terms of preparation, materials used, dealing with the child and the parents as well as the standardized examination technique are presented. In particular, the technical aspects of fluoroscopy devices and criteria for good image quality are discussed. Case studies are used to illustrate the problems of frequent urological diseases., Discussion: The three standard examinations for the detection of vesicoureteral reflux (VUR), radionuclide cystography, contrast-enhanced voiding urosonography and voiding cystourethrography are compared. Their potential for detecting VUR and additional urological pathologies is discussed in detail. Furthermore, the optimized examination technique of voiding cystourethrography is presented. The applicability of the current dose reference values of the German Federal Office for Radiation Protection (BfS) in the daily routine is discussed and the feasibility of the dose reference values is explained., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Vesicoureteral reflux (VUR) is a childhood condition that is usually diagnosed by fluoroscopic voiding cystourethrography (VCUG). Intrarenal reflux (IRR) of infected urine is believed to play an important role in the pathogenesis of reflux‐associated pyelonephritis and subsequent parenchymal scarring and is traditionally depicted by fluoroscopic VCUG. This case series describes the phenomenon of IRR occurring in association with VUR in 4 children as depicted by contrast‐enhanced voiding urosonography. The ability of contrast‐enhanced voiding urosonography to show IRR when it occurs in conjunction with VUR compares favorably to that of fluoroscopic VCUG. [ABSTRACT FROM AUTHOR]

Objectives To elucidate the significance of intrarenal reflux. Methods We retrospectively analyzed 276 patients (age <5 years) with grade III to V vesicoureteral reflux. They were divided into two groups: 55 patients with intrarenal reflux and 221 patients without intrarenal reflux (control group). All patients received low-dose antibiotic prophylaxis. Results The most common initial presentation in both groups was febrile urinary tract infection. On dimercaptosuccinic acid scan, the rate of decreased differential renal function (<40%) was significantly higher in the intrarenal reflux group than in the control group (51% vs 33%, P < 0.05). Breakthrough urinary tract infections were observed in 26 patients (47%) in the intrarenal reflux group and 61 patients (28%) in the control group ( P < 0.01). There was no statistically significant difference regarding spontaneous resolution of reflux, which occurred in nine patients (16%) in the intrarenal reflux group and 32 patients (14%) in the control group. Surgical treatment was selected more often in the intrarenal reflux group ( P < 0.05) because of the high incidence of breakthrough urinary tract infection. Conclusions The rate of spontaneous resolution of high-grade vesicoureteral reflux is similar between patients with and without intrarenal reflux. However, those with intrarenal reflux present are more likely to present a decreased differential renal function and breakthrough urinary tract infections. Consequently, surgical treatment is considered more frequently in cases with intrarenal reflux. Although high-grade vesicoureteral reflux with intrarenal reflux can be treated conservatively, physicians should take into account the higher risk of breakthrough urinary tract infections. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The aim of this study was to evaluate the prognostic significance of intrarenal reflux (IRR) regarding urinary tract infection (UTI), renal scarring and spontaneous resolution after 3 years of follow up. Patients and methods: 33 patients (42 refluxing units) with IRR were compared to 27 children (44 refluxing units) with high-grade vesicoureteral reflux (VUR) without IRR (controls) matched for gender, age and VUR grade. All patients received antibiotic prophylaxis during observation and antireflux surgery was performed in children with recurrent UTI. DMSA scan was performed at study entry, and 18 and 36 months. Results: DMSA scores at entry showed a higher proportion of moderate and severe damage in the IRR group (25/42) compared to the control group (16/44) (Chi squared, P < 0.03). During follow up the incidence of UTI was similar in the two groups, as well as the stability of DMSA scintigraphy and the rate of spontaneous disappearance of the reflux. A similar proportion of patients underwent surgery (18/33 patients with IRR and 13/27 control patients; Chi squared, not significant). Conclusions: Under medical management, the prognosis for IRR is not different from high-grade VUR without IRR. The presence of IRR does not justify more aggressive management than a high-grade VUR without IRR. [Copyright &y& Elsevier]

Purpose: To describe the parenchymal defects in kidneys with intrarenal reflux (IRR) diagnosed using contrast-enhanced voiding urosonography (ceVUS) and 99m Tc-DMSA scintigraphy (DMSA scan)., Materials and Methods: A group of 186 uretero-renal units (URUs) was analyzed using ceVUS and DMSA scans: 47 without vesicoureteral reflux (VUR) (group A) and 139 with VURs, comprising 73 VURs without (group B), and 66 with IRR (group C). VURs included non-dilating (grades I-II), mildly non-dilating (grade III), and non-dilating (grades IV-V) grades. The parenchymal changes were analyzed using a DMSA scan., Results: The median age for VUR diagnosis was 16.5 months in girls, and 8.5 months in boys ( Z = 3.9; p = 0.001). IRR occurred in 51.4% of boys and in 25.9% of girls (χ 2 = 12.4; p < 0.001). The non-dilating VUR occurred in 44% of boys and 24.1% of girls (χ 2 = 7.7; p = 0.005). IRRs characterized upper and lower renal segments (81.8 and 63.6%) and middle segments (33.3%). Both incidence and increase in IRR correlated with the grade of VUR ( p < 0.001). The incidence of reduced DMSA signal was statistically different among groups A + B and C, but not between groups A and B (χ 2 = 32.2; p < 0.001). No statistically significant relationship existed between the reduced DMSA signal and the grade of VUR in group C. The reduced DMSA signal appeared in 9.9% positions in kidneys from group A, 14% from group B, and 32% from group C. Out of all 118 IRRs, 38.1% had reduced and 61.9% had normal DMSA signal. Among 11 parenchymal scars found in all three groups, 2 belonged to group B, 9 to group C, while group A had no scars., Conclusion: The parenchymal changes are the most prominent in the group with IRR, but they do not significantly differ among kidneys with different grades of VUR. VURs of higher grades are associated with a higher incidence of IRR and early clinical presentation. Scars can also appear in lower-grade VURs accompanied by IRR. Boys with VUR have earlier clinical presentation than girls, as they have significantly higher grades of VUR with a higher proportion of IRRs. Therefore, we suggest a subdivision of VURs into those with IRR and abundant parenchymal damage, and those without IRR and less parenchymal damage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Simičić Majce, Arapović, Čapkun, Brdar, Brekalo, Zebić, Barić, Punda, Saraga-Babić, Vukojević and Saraga.)

Purpose: This study evaluated the diagnostic performance of contrast-enhanced voiding ultrasonography (CeVUS) for detecting intrarenal reflux (IRR) and the correlation between CeVUS-detected IRR sites and photon defect sites in acute 99mTc-dimercaptosuccinic acid (DMSA) renal scans in pediatric patients., Methods: Fifty-four kidneys from 27 patients (20 males and seven females; mean age, 5.6±4.1 months) who underwent CeVUS and acute DMSA renal scans for recurrent urinary tract infection (UTIs) or pyelonephritis were included. Pediatric experts compared the results of CeVUS with acute DMSA renal scans., Results: Thirteen renal units (13/54, 24.1%) in 10 patients (nine males and one female; mean age, 6.3±3.7 months; age range, 0 to 13 months) showed vesicoureteral reflux and eight renal units (8/54, 14.8%) demonstrated IRR on CeVUS. Ten renal units in eight patients (six males and two females; mean age, 6.9±1.4 months; age range, 2 to 13 months) showed 19 photon defects on acute DMSA renal scans. Fifty-two renal units (96.3%) showed concordant results, and two renal units (3.7%) showed discordant results between CeVUS and acute DMSA renal scans. IRR accounted for 15/19 (78.9%) photon defects in eight renal units of seven patients using CeVUS. In a per-renal-unit analysis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CeVUS were 80%, 100%, 100%, 95.7%, and 96.3%, respectively., Conclusion: CeVUS showed good performance in detecting IRR, and the IRR sites detected by CeVUS closely correlated with photon defect sites in acute DMSA scans. CeVUS may play an important role in managing patients with recurrent UTIs or pyelonephritis with reduced radiation exposure.

Using an autopsy case of a 59-year-old man with analgesic nephropathy, papillary necrosis, and nephrolithiasis, it is shown that analgesic nephropathy may be complicated by damage resulting from intrarenal urine reflux. The morphologic alterations characteristic of intrarenal and/or pyelointerstitial reflux are caused by high intrapelvic pressure values during episodes of renal colic. Bacterially infected and possibly also sterile urine is then forced into the interstitium, directly within the papillary defect or indirectly via the tubular system after rupture of the tubule. The result is a severe interstitial process with inflammation, destruction, and scarring. [ABSTRACT FROM AUTHOR]

The several patterns of radiographic opacification of the renal parenchyma in urinary tract obstruction and vesico-ureteric reflux are described. Recent descriptions of the detailed morphology of the renal papilla suggest explanations for these appearances. The mechanisms involved and their possible significance are discussed. [ABSTRACT FROM AUTHOR]

Reflux nephropathy is now a generally accepted term to describe small scarred kidneys discovered during childhood; it recognises the close association between this renal lesion and vesicoureteric reflux (VUR). This paper briefly reviews the pathogenic factors involved in reflux nephropathy and suggests that at least two main mechanisms operate: acquired segmental scarring due to intrarenal reflux and congenital maldevelopment (renal dysplasia). The spectrum of renal changes associated with VUR can be usefully divided on this basis and the opportunity to recognise by fetal ultrasound those renal lesions acquired in utero may further enhance our understanding of the congenital maldevelopment group. [ABSTRACT FROM AUTHOR]

The vast majority of small segmentally scarred kidneys seen in childhood are now recognised to be associated with vesicoureteric reflux and the term 'reflux nephropathy' has been accorded general recognition as a description of this renal lesion. With regard to the pathogenic mechanisms responsible for the scarring process, the possible roles of intrauterine renal maldevelopment, bladder dysfunction, functional urinary obstruction and infection in relation to vesicoureteric reflux and the associated phenomenon of intrarenal reflux must all be considered. It is probable that in different clinical circumstances all of these factors may be important to varying degrees and discussion of their contributions to the spectrum of reflex nephropathy is the basis of this communication. [ABSTRACT FROM AUTHOR]

The most frequent complications of non-obstructive vesico-uretero-renal reflux (VUR) are segmental renal scars. These scars are confined to segments with intrarenal reflux which are, in addition, exposed to bacterial infection. Primarily, only gaping collecting duct orifices, confined to compound papillae and mainly situated at the kidney poles, allow intrarenal reflux. Scar contraction and obstruction seem to be able to transform closed collecting duct orifices into gaping ones, thereby enlarging the parenchymal area prone to intrarenal reflux and to renal scarring. Contrary to earlier reports, a recent survey has documented that new scars in children develop with significant frequency beyond 5 years of age. There is a greater tendency for scarring to develop with more severe VUR, but new renal scars can develop with all grades of VUR [27]. Early and adequate antibiotic treatment decreases the extent of scarring. The results of experimental studies in which renal scarring developed in piglets with bladder decompensation resulting from intravesical obstruction but without bacterial infection may be relevant to the few children with proximal urethral valves and hypertonic neurogenic bladders but not to the large number with non-neurogenic detrusor instability or detrusor sphincter dyssynergia. Prospective studies have not shown different recurrence rates of urinary tract infections in medically managed compared with surgically managed children. The frequency of acute pyelonephritic attacks decreased significantly after operation. [ABSTRACT FROM AUTHOR]

Reflux is frequent in infant but uncommon in adult monkeys. Maturation of the ureterovesical junction thus occurs. Infection causes reflux only when the ureterovesical junction has been made marginally competent. Neither vesicoureteral nor intrarenal reflux affects renal function unless either infection or obstruction is present. [ABSTRACT FROM AUTHOR]

The radiographic appearances and dynamics of intrarenal reflux have been defined in an experimental study of the pig's kidney. Intrarenal reflux occurs only with 'refluxing' papillae and is an 'all-or-none' phenomenon when the threshold figure of 10-15 mm Hg is exceeded. Increasing intrapelvic pressure leads to increasing density of the radiographic shadow but new areas of intrarenal reflux are not produced. [ABSTRACT FROM AUTHOR]

Intrarenal reflux in piglets has been related to the morphology of individual renal papillae. These studies show that intrarenal reflux occurs only in the presence of the more extensively fused papillae found predominantly at the upper and lower poles of the kidney. These papillae each have a flattened or concave area cribrosa with large open papillary ducts which cannot be closed by a rise in intracalyceal pressure. In contrast intrarenal reflux never occurs into cone-shaped papillae seen most commonly in the mid-zone of the kidney, which have easily closed, oblique, slit-like papillary duct orifices. The significance of these findings in relation to the genesis of chronic pyelonephritic scarring is discussed. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the diagnostic performance of contrast-enhanced voiding urosonography (ce-VUS) using a second-generation ultrasound contrast agent for the diagnosis of vesicoureteral reflux (VUR) and intrarenal reflux (IRR), and compared it with that of standard fluoroscopic voiding cystourethrography (VCUG)., Methods: Thirty-two consecutive children from April to October 2019 were included in this study. ce-VUS and VCUG were performed simultaneously by two operators with intravesical infusion of a mixture of ultrasound contrast medium, iodinated contrast medium and water. Two pediatric radiologists independently reviewed the ce-VUS and VCUG images and reported the presence and degree of VUR (grades I-V), and the presence and type of IRR., Results: Twenty-seven of 63 urinary systems showed VUR. Interobserver agreement for VUR grading was very good for both examinations (κ=0.87; 95% confidence interval [CI], 0.82 to 0.92 for ce-VUS and κ=0.92; 95% CI, 0.87 to 0.96 for VCUG). The detection rate of VUR showed no significant difference between the two examinations (P=0.370). Four cases of VUR were missed on ce-VUS, while one case of VUR was missed on VCUG. All four false-negative cases on ce-VUS were grade 1 VUR. The two examinations showed very good agreement regarding VUR grading (κ =0.89; 95% CI, 0.81 to 0.96). IRR was more frequently detected with ce-VUS than with VCUG (10 cases with ce-VUS vs. 3 cases with VCUG, P=0.016)., Conclusion: ce-VUS showed very good agreement with VCUG for detecting grade 2 VUR and above, while grade 1 VUR was sometimes missed with ce-VUS. IRR was more frequently detected with ce-VUS than with VCUG.

The objective of this case report is to demonstrate the possibility of visualizing intrarenal reflux (IRR) in children using contrast-enhanced harmonic voiding urosonography (VUS). A 10-month-old girl underwent VUS as part of the work-up of acute pyelonephritis of the right kidney. Before and after intravesical administration of US contrast medium (Levovist) the urinary tract was scanned in harmonic imaging mode. Bilateral vesicoureteric reflux was detected (right grade IV, left grade III). Moreover, at the height of the reflux the right kidney parenchyma turned markedly echogenic, corresponding to massive IRR. The voiding cystourethrography that followed confirmed the results of the VUS. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to analyze the incidence of intrarenal reflux (IRR) among vesicoureteral refluxes (VURs), diagnosed by contrast-enhanced voiding urosonography (ceVUS), to define VURs which are positive to IRR and their locations in the kidney. Materials and Methods: Seventy patients with VURs, including 103 uretero-renal units (URUs) with VURs of grades II-V (37 URUs were excluded because of renal anomalies or absence of VUR) were examined with ceVUS due to recurrent febrile UTI or first febrile UTI accompanied by abnormalities on renal ultrasonography. Patients were examined on GE Logiq S8 ultrasound machine, using second generation of ultrasound contrast agent. Results: Out of 103 VURs, 51 (49.51%) had IRR regardless the grade of VUR, showing increase in IRR incidence with VUR severity ( p < 0.0001). The median age at the time of IRR diagnosis was 5 months (IQR, 3-14.3), whereas in patients without IRR, it was 15.5 months (IQR, 5-41.5), ( p = 0.0069). IRR was most common in superior pole (80%), followed by inferior pole (62.7%), and middle segments (37%), and to all segments (27%) ( p < 0.0001). Conclusion: In the present study, patients with IRR-associated VUR showed earlier clinical presentation. The distribution of IRRs corresponded to the natural distribution of composed papillae types II and III, while the incidence of IRR increased with severity of VUR. Further clinical studies may point to the importance of considering IRR in the future classification of VUR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Simicic Majce, Arapovic, Saraga-Babic, Vukojevic, Benzon, Punda and Saraga.)

The morphology of the renal papillae was studied in a series of necropsy kidneys from infants and young children, and related to experimental data obtained in piglets. As in the piglet, extensively fused papillae of the type associated with intrarenal reflux occurred almost exclusively at the upper and lower poles of the kidney. However, the incidence of this kind of papilla was much lower in the children's kidneys, and in over a quarter of the specimens examined only cone-shaped papillae were found; this latter type of papilla is never associated with intrarenal reflux in the piglet. [ABSTRACT FROM AUTHOR]